tbuckley/cabot-search huggingface dataset:
Abstract 13859: The Omics Signature of Human Pericardial Fluid Exosomes Reveals the Therapeutic Potential of APAF-1 Inhibition in Ischemic Heart Disease
Authors: Mohamed Bellahcene, Jaimy Saif, Moumita Sarkar, Maryam Anwar, Sezin Aday, Sunny Sedani, Yingshu Guan, Aranzazu Chamorro-Jorganes, Inigo Ruiz Polo de Lara, Kate Heesom, gianni angelini, Prakash Punjabi, Dan Peer, Costanza Emanueli
Journal: Circulation (2023)

Background: The human pericardial fluid (PF) contains heart-derived small extracellular vesicles (sEVs) able to induce vascular responses via microRNA (miR) transfer. People with diabetes (DM) are particularly at risk of severe ischemic heart disease (IHD) and might require personalized therapeutic treatment. Hypothesis: The PF-sEVs molecular profiling supports the identification of clinical-relevant therapeutic targets. Aims: 1) To characterize PF-sEVs of IHD patients with/out type-2 DM (T2DM) in comparison to controls; 2) to validate the emerging therapeutic target candidates. Methods: PF samples (n=12/group) were collected during cardiac surgeries, namely CABG (for IHD with/out DM groups) and mitral valve repair (non-IHD, non-DM control group). sEVs were prepared (SEC), quality controlled (Nanosight and Exoview) and submitted to untargeted proteomics and microRNA array (Exiqon) or validation experiments. miRNA-target prediction methods and integration of proteomics and transcriptomics via networks identified differentially expressed pathogenic proteins and their putative endogenous miRNA regulators. The emerging dysregulated miRNA/protein axis was investigated in vitro and in mice with myocardial infarction (MI) and with/out diet-induced T2DM. Results: the PF-EVs of IHD patients with DM showed increased APAF-1 and reduced let-7b-5p, a miR which we have demonstrated to repress APAF-1 by direct 3’-UTR-binding. Exposure of endothelial cells (ECs) to DM and IHD-mimicking culture conditions increases APAF-1 level, triggering apoptosis and reducing angiogenesis. The phenotype of ECs kept under disease-mimicking conditions was rescued by APAF-1 silencing (siRNAs) and by supplementation with either healthy PF-EV or LNPs carrying let-7b-5p as sole miR cargo. The synthetic APAF-1 inhibitor ZYZ-488 improved post-MI cardiac function (Vevo3100 echocardiography), increased capillary density and reduced EC apoptosis in the peri-infarct area of diabetic and non-diabetic mice of both sexes. Conclusions: PF-EVs represent a novel and privileged source for the discovery of clinical-relevant therapeutic targets. APAF-1 inhibition holds value for post-ischemic cardiac protection and repair, including in diabetic people.
Abstract 19151: Late Gadolinium Enhancement (LGE) in Recurrent Pericarditis Patients on Il-1 Blockers and Standard Anti-Inflammatory Therapy
Authors: Alveena B Syed, Abdullah Yesilyaprak, Ushasi Saraswati, Aqieda Bayat, Paul C Cremer, Allan L Klein
Journal: Circulation (2023)

Introduction: Recurrent pericarditis is defined as the recurrence of pericarditis after a symptom-free interval of 4-6 weeks. Our study aimed to investigate the improvement in the late gadolinium enhancement on cardiac resonance imaging (CMR) in recurrent patients on IL-1 blockers and standard anti-inflammatory therapy. Hypothesis: We hypothesize that patients on IL-1 inhibitor show a better improvement of LGE on CMR in recurrent pericarditis. Methods: This is a retrospective comparative cohort study of 37 recurrent pericarditis patients on IL-1 inhibitor and 107 recurrent pericarditis patients on standard anti-inflammatory therapy. We included patients with LGE tracing and compared both groups. Patients were treated for at least 12 months and were followed for a duration minimum of 12 months. Results: The patients' mean age in the IL-1 inhibitor group was 51.16 ±16, and the standard therapy group was 54.26 ± 14.32. Patients had a median baseline ESR of 5 mm/hr and median hs-CRP of 2.2 mg/L in the IL-1 inhibitor group and a median baseline ESR of 7.5 mm/hr and median hs-CRP of 1.5 mg/L in the standard therapy group. At baseline, patients in the IL-1 inhibitor group had 5.4% none LGE, 43.24% mild LGE, 37.83% moderate LGE, and 13.5% severe LGE. Over the follow-up of 12-24 months, IL-1 inhibitor patients had improvement in LGE, with 35.13% of patients having none LGE and 64.86% having mild LGE. In the standard group, 27.1% had none LGE, 54.2% had mild LGE, 15.88% had moderate LGE, and 2.8% had severe LGE at baseline. Over 12-24 months follow-up, standard therapy group patients had some improvement as well as worsening of LGE in some patients, with 35.51% having none LGE, 59.81% having mild LGE, and 4.6% having moderate LGE. Conclusions: IL-1 inhibitors serve as a competitive antagonist of IL-1 cytokine and block its pro-inflammatory functions. Pericardial delayed enhancement is significant in determining disease course and improvement in patients with pericarditis.
Abstract 13881: Coronary Artery Calcium as a Risk Marker in Patients With Myocardial Infarction but Without Standard Modifiable Risk Factors (SMuRF-Less)
Authors: Jeffrey L Anderson, Stacey Knight, Li Dong, Heidi T May, Viet T Le, Tami L Bair, Kirk U Knowlton
Journal: Circulation (2023)

Introduction: Recent publications have reported that myocardial infarction (MI) patients (pts) without standard modifiable risk factors (SMuRF-less) are surprisingly common (14-27%) and have a notable risk of adverse outcomes. These reports raise the question of how these pts can be identified in advance and provided with effective preventive therapies (e.g., statins, aspirin). Methods: Pts presenting between 2001-2021 to Intermountain Healthcare catheterization laboratories with a diagnosis of MI were included if they also had a coronary artery calcium scan (CACS) by computed tomography within 2 years. SMuRF included a clinical diagnosis of, or treatment for, hypertension, hyperlipidemia, diabetes, and/or smoking. The co-primary endpoints for this study were the proportion of patients with an elevated (&gt;50%ile) CACS score (MESA criteria) and the presence of an indication for statin therapy with or without aspirin (i.e., &gt;=75%ile score or CAC&gt;=100 AU). Major adverse cardiovascular event (MACE) outcomes at 60-days and long-term were evaluated and compared to MI pts with SMuRF. Results: We identified 429 MI pts with a concurrent CACS, of which 60 were SMuRF-less and 369 had SMuRF. The 2 groups were similar in age, sex, most risk factors, and interventions, but fewer SMuRF-less pts had a history of heart failure or a family history (Table 1). SMuRF-less pts had a high prevalence and an increased percentile of CAC (82% &gt;=50%ile; median, 80%ile;), and 77% met criteria for preventive therapy. Pts with SMuRF, as expected, had high CAC scores and percentiles (Table 1). Outcomes were more favorable for SMuRF-less status (Table 2A) and for lower CAC scores (Table 2B). Conclusions: Despite absence of SMuRF, SMuRF-less pts presenting with an MI have a high prevalence and percentile of CAC. Wider application of CACS, to include those without SMuRF, appears promising as a method to identify an additional at-risk population for consideration of preventive therapy.
Abstract 16921: The Capture of the Left Conduction System Appears to Be Essential for Left Bundle Branch Area Pacing to Provide a Greater Acute Hemodynamic Response Than Biventricular Pacing
Authors: Lukas Poviser, Petr Waldauf, Petr Stros, Jana Vesela, Vlastimil Vondra, Zachary Whinnett, Josef Kautzner, Karol Curila
Journal: Circulation (2023)

Introduction: Left bundle branch area pacing (LBBAP), which includes left bundle branch pacing (LBBP) and left septal myocardial capture (LVSP), is a novel alternative of cardiac resynchronization therapy (CRT). However, it is unknown whether the left conduction system capture is required or whether LV septal capture only is sufficient in patients with a CRT indication. Hypothesis: To study the effect of biventricular (Biv) CRT, LBBAP, and, more specifically, LBBP and LVSP on the effectivity of LV performance using a dedicated protocol of blood pressure measurements. Methods: Patients with QRSd ≥ 130 ms of nonRBBB morphologies and an indication for CRT were included. During implantation, the leads were placed in the RV apico-septum, lateral/posterolateral branch of the coronary sinus, and the left septal area to obtain LBBAP. LBBAP was further classified as LBBP or LVSP during decremental output pacing. The acute hemodynamic response was calculated from the changes in the systolic blood pressure measured invasively from the peripheral artery using a high-precision protocol with multiple transitions between the tested pacing configurations. Results: CRT was attempted in 25 consecutive patients with an average age of 68 years. Biv CRT and LBBAP were successful in 23 and 24 patients, respectively. LBBP was achieved 17 and LVSP 13 times (in 6 patients, both capture types were observed). Eight patients had ischemic cardiomyopathy, mean LVEF was 30 ± 6 %, and QRSd during spontaneous rhythm was 174 ± 18 ms. Both Biv CRT and LBBAP significantly reduced QRSd (51 ± 24 ms and 47 ± 22 ms) and resulted in an increase of systolic blood pressure (8 ± 0 mmHg for Biv CRT, and 11 ± 0 mmHg, for LBBAP; p &lt; 0.001 for both) compared to right ventricular pacing. LBBAP increased systolic blood pressure more than Biv CRT (3 ± 0 mmHg; p &lt; 0.001). This was mainly due to a significant increase in blood pressure during LBBP compared to Biv CRT (5 ± 1 mmHg; p &lt; 0.001), while no difference was observed between LVSP and Biv CRT (1 ± 0 mmHg; p = 0.174). Conclusions: In consecutive patients with CRT indication, LBBAP improved acute hemodynamic response more than Biv CRT. Capturing the left conduction system appears to be essential for LBBAP to outperform Biv CRT.
Abstract 16090: Human Chart Abstraction Combined With Electronic Medical Record Programmed Queries Improves Identification of Patients With Cardiac Implanted Electronic Devices
Authors: Gabriela Narowska, Shivalika Khanduja, Edward R Horton, chethan gangireddy, Eman A Hamad, Colleen M Pawlowski, Kim Behrens, Glenn J Whitman, Isaac R Whitman
Journal: Circulation (2023)

Background The Society of Thoracic Surgery cardiac surgery database (STSD) is used for quality improvement and research. The STSD relies on human chart abstraction (STS-HA) to accurately identify cardiac patients with existing Cardiac Implanted Electronic Devices (CIED’s). Perioperative CIED management may impact surgical outcomes, yet the sensitivity of the STS-HA for CIED patients is unknown. Methods All 7 major STS cardiac surgeries performed at Johns Hopkins Hospital (JHH) and Temple University Hospital (TUH), between 7/2017 and 6/2022, were assessed for the presence of a CIED. CIED patients were identified using both STS-HA and a programmed EMR (Epic) reports (EMR-pro) relying on CPT codes, problem lists, structured data elements, and CIED interrogation reports. The presence of existing CIED in patients was confirmed by same-day chest imaging, which is not uniformly searchable using EMR-pro. McNemar’s chi square test was used to compare the sensitivity of STS-HA with EMR-pro to identify preoperative patients with existing CIED’s. Results Using the STSD, we identified 4770 surgical patients across both institutions during the study period (JHH n= 2627, TUH n=2143), of whom 167 patients had CIED’s (3.5%; JHH 77 (2.9%), TUH 90 (4.2%). Of these, STS-HA identified 144 (86.2% pooled sensitivity) as having existing CIED’s (JHH 69, 89.6%; TUH 75, 83.3%). EMR-pro identified 164 patients (98.2% pooled sensitivity; JHH 77, 100%; TUH 87, 96.7%). Each of the 3 TUH patients identified by STS-HA but not by the EMR-pro had CIED documentation in paper chart scans. The pooled sensitivity of EMR-pro was better than that of STS-HA in identification of CIED’s at the time of surgery (p&lt;0.0001). Discussion The programmed EMR algorithm’s superior sensitivity to human abstraction in identifying cardiac surgical patients with existing CIED’s is an important enhancement in identifying this population. This improvement in sensitivity illustrates the power of EMR programmed reports to address the unreliability of human chart abstraction. Understanding the inherent limitations of the STS database and improving it are essential to the interpretation of past STSD based research and improving the reliability of STSD based studies performed in the future.
Abstract 19161: EchoMap Automatically Maps Echocardiogram Report Text to Ontology
Authors: Sara Rizvi, Ramya Ramesh, Vibhor Sehgal, Brinda Gurusamy, Jeffrey Tran, G. Burkhard Mackensen, Rima Arnaout
Journal: Circulation (2023)

Background: Big data has the potential to revolutionize echocardiography by enabling novel research and rigorous, scalable quality improvement. Text reports are a key part of such analyses. Currently, echocardiogram reports include both structured and free text and vary across institutions, hampering attempts to mine text for useful insights. Natural language processing (NLP) can help and includes both non-deep learning and deep-learning (e.g., large language model, or LLM) based techniques. Challenges to date in using echo text with LLMs include small size, domain-specific language, and high need for accuracy and clinical meaning in model results. Hypotheses: We tested whether we could map echocardiography text to a structured ontology using NLP. Methods: We developed a three-tier ontology for the echocardiographic anatomic structures, functional elements, and descriptive characteristics in an adult transthoracic echocardiogram using 919 sentences from UCSF’s structured echocardiogram report text. We tested LLM fine-tuning as well as non-LLM techniques to map echocardiography sentences to this ontology. Two-hundred twenty-eight UCSF sentences served as an internal test set. Additional test datasets included free text from UCSF reports; structured text sentences from two other hospitals; and sentences from reports representing 17 additional hospitals. Results: Despite all adhering to clinical guidelines for reporting, there were notable differences by institution in what structural and functional information was included in structured reporting. A non-LLM hierarchical model performed best in mapping sentences to the ontology, with internal test accuracy of 96% for the first level of the ontology, 91% for the second level, and 77% for the third level. Echomap retained good performance across diverse datasets and displayed the ability to extrapolate to ontological terms not initially included in training. Conclusions: We show that non-LLM NLP methods can achieve good performance and may be especially useful for small, specialized text datasets where clinical meaning is important. These results highlight the utility of a high-resolution, standardized cardiac ontology to harmonize reports across institutions.
Abstract 16941: Breast Artery Calcification for Primary Prevention of Major Adverse Cardiovascular Outcomes: A New Risk Stratification Tool for Women
Authors: Thara S Ali, Roberta diFlorio-Alexander, Judith Austin-Strohbehn, Thomas S Truglio, Hemant Kulkarni, Amit Amin, Cynthia C Taub
Journal: Circulation (2023)

Introduction: Reductions in cardiovascular mortality among women lag behind men. There is a critical need for improved primary prevention of major adverse cardiovascular events (MACE) in women. We examined if breast artery calcification (BAC), detected on screening mammograms, prognosticates long-term MACE. Methods: In this retrospective study of consecutive women age 40-75 years without coronary disease from 2011-12, followed for 10 years at Dartmouth-Hitchcock Medical Center, we recorded baseline mammograms, clinical parameters and 10-year MACE risk was estimated via the pooled cohort equation (PCE). The association of BAC and MACE was examined by a multivariable, interactive logistic regression model with MACE as dependent variable, adjusting for confounders and an interaction of BAC with 3 strata of PCE predicted risk: low (&lt;5%), moderate (5-7.5%) and high (&gt;7.5%). The primary endpoint was MACE over 10 years. Results: Among 1216 women, 19% had BAC. Women with BAC were older, had more hypertension and diabetes, and a higher baseline PCE score. Over 10 years of follow-up, 21% of women with BAC developed MACE compared to 11% women without BAC (p&lt;0.001). This association was independent of risk factors and statin use. Among women with low (&lt; 5%) risk of MACE, those with BAC had an 18% incidence of MACE, compared to 7% in women without BAC (OR 2.8, 95% CI 1.5 - 5.0) (Fig 1A). The incremental increase in MACE in patients with BAC decreased with higher PCE-predicted risk. Peak interaction occurred at a PCE-predicted risk of 10% (Fig 1B). Among women with a PCE-predicted risk &lt;10%, BAC was a strong predictor of MACE with an attributable fraction of 20% (Fig 1B). Conclusions: BAC is a strong, independent predictor of MACE, particularly in women at low risk by PCE. Although PCE is used widely to risk stratify women for MACE, our study suggests it severely underestimates risk in women with a low PCE score. Further prospective trials are needed to validate these findings.
Abstract 19135: Deep Learning Model for Detection of Conduction Disorders and Arrhythmias From PDF Outputs of Commercially Available Wearable Devices
Authors: Veer Sangha, Akshay Khunte, Lovedeep S Dhingra, Evangelos K Oikonomou, Rohan Khera
Journal: Circulation (2023)

Background: Wearable and portable devices with ECG capabilities have the potential to enable broad AI-based screening for clinical disorders, but models trained on single-lead signals are limited by challenges accessing the raw signal data from proprietary systems. Additionally, wearable ECGs have traditionally been limited to diagnosing only a few rhythm disorders. Methods: From 385,601 clinical ECGs performed at Yale during 2015-2021, we extracted lead I data, and simulated wearable PDF outputs from commercial wearable devices. Gold-standard diagnosis statements from cardiologists accompanying these ECGs were processed and used to generate 41 clinical labels. We developed a multilabel model to predict these labels from wearable-adapted PDF outputs using an EfficientNet-B3 convolutional neural network with self-supervised pretraining. The model deployment pipeline was optimized to segment and process PDF outputs across all commercially available devices as inputs to the model (Fig A &amp; B). Results: In a held-out test set of 11,611 ECGs, the model accurately detected a diverse set of disorders. For the rhythm disorders sinus tachycardia, sinus bradycardia, atrial fibrillation, atrial flutter, premature atrial contraction, and premature ventricular contraction, the model had AUROCs of 0.99, 0.98, 0.98, 0.93, 0.96 and 0.95 respectively. For the conduction disorders left bundle branch blocks, right bundle branch blocks, 1 st and 2 nd degree AV blocks, the model had AUROCs of 0.98, 0.97, 0.96 and 0.95, respectively. Finally, for key disorders such as STEMI, LVH, and low limb-lead voltage, the model had AUROCs of 0.81, 0.86, and 0.77, respectively (Fig C). Conclusions: We developed and validated a deep learning model to identify conduction disorders and arrhythmias from PDF image outputs of wearable and handheld single-lead devices. This approach allows for automated and easily accessible insights into wearable and portable ECGs at the point of care.
Abstract 12515: Effect of Intravenous Iron Therapy in Patients With Heart Failure and Iron Deficiency: A Meta-Analysis of Randomized Controlled Trials
Authors: Vikash Jaiswal, Akash Jaiswal, Vibhor Agrawal, Song Peng Ang, Kriti Kalra, Himanshi Bisht, Apoorva Tripathi, Monodeep Biswas
Journal: Circulation (2023)

Background: Iron deficiency is a frequently observed comorbidity in patients with chronic heart failure (HF). Present guidelines strongly advocate for the routine screening of iron deficiency anemia in all HF patients. Numerous randomized controlled trials (RCTs) have examined the efficacy and safety of intravenous iron-carbohydrate complexes as a supplementation approach for patients with HF with reduced ejection fraction (HFrEF). Nevertheless, there exists a necessity to systematically synthesize the evidence derived from these RCTs through a comprehensive meta-analysis. Methods: A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized. Results: A total of 14 RCTs with 3597 patients were included in the analysis. The pooled analysis demonstrated a significant reduction in the composite outcome of cardiovascular death or hospitalization for worsening HF (OR 0.55, 95% CI= 0.45, 0.67; p &lt; 0.001). Similarly, the composite outcome of all-cause death or cardiovascular hospitalization showed a significant benefit with intravenous iron supplementation (OR 0.42, 95% CI= 0.28, 0.62; p &lt; 0.001). Moreover, the analysis indicated a significant decrease in hospitalizations for HF among patients receiving IV iron (OR 0.49, 95% CI= 0.32, 0.75; p &lt; 0.001). However, no statistically significant difference was observed in all-cause mortality (OR 0.90, 95% CI= 0.74, 1.10; p = 0.31) and cardiovascular mortality (OR 0.85, 95% CI= 0.68, 1.05; p = 0.14) between the two groups. Conclusion: The evidence from this meta-analysis underscores the significance of incorporating IV iron therapy in iron-deficient patients with systolic HF as it demonstrates significant improvements in patient outcomes.
Abstract 19142: Is Malnutrition Associated With Worse Outcomes in Patients With Acute Decompensated Heart Failure (ADHF)? ; Insights From Nationwide Inpatient Sample 2015-2020
Authors: Nadish Garg, Krishna Prasad Kurpad, Aditya Desai, Darshi Desai, Sanjay Mehta, Padmini Varadarajan, Ramdas G Pai
Journal: Circulation (2023)

Introduction: Is Malnutrition associated with worse outcomes in patients admitted with acute decompensated heart failure? Insights from nationwide inpatient sample 2015-2020 Hypothesis: Heart Failure affects &gt;5 million US patients resulting in &gt;1 million annual hospitalizations due to Acute Decompensated Heart Failure (ADHF). The impact of malnutrition on hospitalized patients with ADHF is not well described. Patients with heart failure are prone to malnutrition because of reduced intake, cytokine dysfunction, and increased basal metabolic rate. We aim to assess the effect of malnutrition on hospital outcomes in ADHF. Methods: Using the NIS database we identified all the patients who were admitted for ADHF with history of heart failure with reduced ejection fraction from 2015-2020. Predictors and effects of malnutrition were studied using univariate and multivariate models. Results: A total of 4,224,869 patients were admitted for ADHF from 2015-2020 among which 253,915 patients had associated malnutrition. Baseline characteristics and comorbidities are outlined in the table below. Patients with malnutrition had higher inpatient mortality (9.6% vs 3.61% p-value:0.0000), a longer length of stay (10.8 days vs 5.9 days p-value: 0.0000), doubling of the cost of care (147485 USD vs 74077 USD p-value:0.001). After adjusting for baseline co-morbidities patients with malnutrition had 2 times higher mortality (Odds ratio: 2.01, p-value: 0.0001) Conclusions: Our study demonstrates that Malnutrition in ADHF patients results in higher mortality, longer length of stay, and higher costs of care. This highlights the importance of optimizing of nutritional status in these patients.